BIOSPECIMEN CORE ? CORE D: PROJECT SUMMARY/ABSTRACT The BIOCARD study is a longitudinal, observational study of 349 individuals who were cognitively normal and primarily middle aged (mean age=57.1) at enrollment. The subjects have now been followed for up to 27 years. The overall objectives of the project are to further advance the study of preclinical Alzheimer?s disease by: (1) clarifying the pattern and rate of change in AD biomarkers (including those based on CSF, blood, MRI, and PET imaging) and cognition; the biomarkers to be studied include several promising novel biomarkers derived from blood, CSF and brain imaging. (2) maximizing our data by working collaboratively with several research groups who have comparable data, and (3) providing a publicly accessible data, brain scans, and biological specimens, for researchers in the field. To accomplish these goals we established 7 Cores and, with this application, are also including 2 projects. The Biospecimen Core (Core D) is responsible for overseeing the acquisition and analysis of cerebrospinal fluid and blood in the BIOCARD study participants. The specific aims include: (1) to collect, catalog and store cerebrospinal fluid (CSF) and blood specimens from the participants, (2) to perform state-of-the-art CSF assays of the specimens collected in the study participants, (3) to examine the effect of pre-analytic variables on the CSF assays of Abeta42, tau and p- tau, (4) to measure several additional assays in CSF, including synaptojanin1 (SynJ1), klotho and soluble TREM2 (sTREM2), (5) to integrate the CSF and blood measures generated by Core D and Project 1 with the clinical, cognitive, MRI and PET measures collected in the other Cores, (6) and to continue to share data derived from the biospecimens in this study with investigators in the field, and to share specimens, as appropriate.